ArticleAntimicrobial agents and chemotherapy2011
New Fks hot spot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Fusarium species,Scedosporium species, and Lomentospora prolificans: A systematic review to inform the World Health Organization priority list of fungal pathogens.Medical mycology · 2024Pooled it
- Amphotericin B resistance inAntimicrobial agents and chemotherapy · 2026Article
- Amphotericin B Resistance inbioRxiv : the preprint server for biology · 2026Article
- Article
- Mutational landscape and molecular bases of echinocandin resistance in Saccharomyces cerevisiae.Genetics · 2026Article
- Deciphering the multidrug resistance paradigm inAntimicrobial agents and chemotherapy · 2026Review
- A Candidozyma (Candida) auris-Optimized Episomal Plasmid-Induced Cas9-Editing System Reveals the Direct Impact of the S639F-Encoding FKS1 Mutation.The Journal of infectious diseases · 2025Article
- FungAMR: a comprehensive database for investigating fungal mutations associated with antimicrobial resistance.Nature microbiology · 2025Article
- Tn-seq screens inmSphere · 2025Article
- Fungal β-1,3-glucan synthase: a review of structure, mechanism, and regulation.FEMS yeast research · 2025Review
- Unlocking the potential of experimental evolution to study drug resistance in pathogenic fungi.npj antimicrobials and resistance · 2024Review
- Scedosporiosis and lomentosporiosis: modern perspectives on these difficult-to-treat rare mold infections.Clinical microbiology reviews · 2024Review
- Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights.Journal of fungi (Basel, Switzerland) · 2024Review
- Review
- Diagnosis of invasive fungal infections: challenges and recent developments.Journal of biomedical science · 2023Review
- Article
- Analysis of the Localization ofInternational journal of molecular sciences · 2023Article
- Caspofungin resistance in Candida albicans: genetic factors and synergistic compounds for combination therapies.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2022Review
- Benzylic Dehydroxylation of Echinocandin Antifungal Drugs Restores Efficacy against Resistance Conferred by Mutated Glucan Synthase.Journal of the American Chemical Society · 2022Article
- Jerveratrum-Type Steroidal Alkaloids Inhibit β-1,6-Glucan Biosynthesis in Fungal Cell Walls.Microbiology spectrum · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two "hot spot" regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new "hot spot 3" in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.